Breast Cancer
Conditions
Brief summary
The purpose of this research study is to find out what effects (good and bad) docetaxel/cyclophosphamide (brand names: Taxotere and Cytoxan, or TC) plus trastuzumab (brand name: Herceptin, or H) has HER2+ breast cancer.
Interventions
DRUGTaxotere
On Day 1 of each 21-day cycle for a total of 4 cycles, patients will receive, in this order: docetaxel 75 mg/m2 IV (over 1 hour), plus cyclophosphamide 600 mg/m2 IV (over 15-30 minutes), plus weekly trastuzumab 4 mg/kg IV (loading dose, over 90 minutes Day 1, Cycle 1 only) and 2 mg/kg IV (over 30-60 minutes on Days 1, 8, and 15) thereafter. Once 4 cycles of TC+H have been received, patients will continue with trastuzumab 6 mg/kg every 3 weeks to complete 1 year of anti-HER2 therapy as per the current standard of care. The anticipated time to study completion is 5 years.
DRUGCytoxan
On Day 1 of each 21-day cycle for a total of 4 cycles, patients will receive, in this order: docetaxel 75 mg/m2 IV (over 1 hour), plus cyclophosphamide 600 mg/m2 IV (over 15-30 minutes), plus weekly trastuzumab 4 mg/kg IV (loading dose, over 90 minutes Day 1, Cycle 1 only) and 2 mg/kg IV (over 30-60 minutes on Days 1, 8, and 15) thereafter. Once 4 cycles of TC+H have been received, patients will continue with trastuzumab 6 mg/kg every 3 weeks to complete 1 year of anti-HER2 therapy as per the current standard of care. The anticipated time to study completion is 5 years.
DRUGHerceptin
On Day 1 of each 21-day cycle for a total of 4 cycles, patients will receive, in this order: docetaxel 75 mg/m2 IV (over 1 hour), plus cyclophosphamide 600 mg/m2 IV (over 15-30 minutes), plus weekly trastuzumab 4 mg/kg IV (loading dose, over 90 minutes Day 1, Cycle 1 only) and 2 mg/kg IV (over 30-60 minutes on Days 1, 8, and 15) thereafter. Once 4 cycles of TC+H have been received, patients will continue with trastuzumab 6 mg/kg every 3 weeks to complete 1 year of anti-HER2 therapy as per the current standard of care. The anticipated time to study completion is 5 years.
Sponsors
Sanofi
US Oncology Research
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
A woman will be eligible for inclusion in this study if she meets all of the following criteria: * Has HER2+ (IHC staining of 3+ \[uniform, intense membrane staining of \>30% of invasive tumor cells\], or a FISH result of .6 HER2 gene copies per nucleus or a FISH ratio \[HER2 gene signals to chromosome 17 signals\] of \>2.2; patients with equivocal FISH ratio results 1.8-2.2 are also eligible if 3+ IHC) (Appendix IX); Stage I, IIA, IIB, or IIIA T1-3N1-3M0 disease. At the discretion of the Treating Physician, patients with 4+ nodes with other factors such as patient choice, older age, preexisting cardiac disease with normal MUGA or ECHO may be enrolled into a separate subgroup. * Has operable, histologically confirmed, invasive carcinoma of the breast. * Has known ER and PR status * Has adequate tumor specimen available for FISH analysis of TOP2A status (See Appendix VII) * Has had no prior chemotherapy unless it was given \>5 years ago for breast cancer or other cancer * Has an ECOG Performance Status (PS) 0-1 * Age \>18 to \<70 years old. * Has laboratory values of: See protocol for specific details * Has aspartate aminotransferase (AST) or alanine aminotransferase (ALT) and alkaline phosphatase (ALP) within the ranges shown below. In determining eligibility the more abnormal of the 2 values (AST or ALT) should be used. See protocol for specific details * Has complete surgical resection of the primary breast tumor: either lumpectomy or mastectomy with sentinel lymph node or axillary dissection. * It has been \<84 days since the date of definitive surgery, and there is adequate wound healing as determined by the Treating Physician * Has no evidence of metastatic disease by physical examination and x-ray; appropriate scans as needed by each individual patient (eg, bone scan; abdominal, chest CT; PET or PET/CT; ultrasound; or MRI should indicate no evidence of metastatic disease. * Has normal cardiac function as evidenced by a LVEF \>50%, but must be within normal limits (WNL) by institutional standard, as determined by multiple gated acquisition (MUGA) scan. An echocardiogram (ECHO). The same modality must be used throughout the study to evaluate LVEF. Ejection fraction (EF) as determined by ECHO must be WNL by institutional standard. * Has a negative serum pregnancy test within 7 calendar days prior to registration (female patients of childbearing potential \[not surgically sterilized and between menarche and 1 year postmenopause\]). * If fertile, patient has agreed to use an acceptable method of birth control (barrier contraceptive) to avoid pregnancy for the duration of the study and for a period of 3 months thereafter * Has signed a Patient Informed Consent Form * Has signed a Patient Authorization Form
Exclusion criteria
A woman will be excluded from this study if she meets any of the following criteria: * Has any evidence of disease following complete surgical resection of the primary tumor and metastatic workup * Has Stage IIIB breast cancer (T4 disease; ie, patients with fixed tumors, peau d'orange skin changes, skin ulcerations, or inflammatory changes). * Has Stage IV breast cancer (M1 disease on TNM staging system) * Had prior chemotherapy for breast cancer or other cancer within the last 5 years (no neoadjuvant chemotherapy in this study is permitted) * Has a history of severe hypersensitivity reaction to drugs formulated with polysorbate 80 * Has had a myocardial infarction (MI) within 6 months of trial enrollment, or has New York Heart Association (NYHA) Class II or greater heart failure (see Appendix III), uncontrolled angina, severe uncontrolled ventricular arrhythmias, clinically significant pericardial disease, or electrocardiographic evidence of acute ischemic changes * Has abnormal baseline MUGA (or ECHO) (\<50%, or less than institutional LLN) * Is receiving concurrent immunotherapy, hormonal therapy, or radiation therapy. Adjuvant hormonal therapy, if needed, may be given during radiation therapy and during treatment with trastuzumab after completion of chemotherapy. * Is receiving concurrent investigational therapy or has received such therapy within the past 30 calendar days * Has peripheral neuropathy \>Grade 1 * Has a serious uncontrolled intercurrent medical or psychiatric illness, including serious viral (including clinically defined AIDS), bacterial or fungal infection; or history of uncontrolled seizures, or diabetes, or CNS disorders deemed by the Treating Physician to be clinically significant, precluding informed consent * Has active hepatitis B or hepatitis C with abnormal liver function tests (LFTs) or is known to be HIV positive * Has a history of other malignancy within the last 5 years (except cured basal cell carcinoma of skin and carcinoma in situ of uterine cervix), which could affect the diagnosis or assessment of any of the study drugs * Is an obese patient to whom the Treating Physician would not be comfortable administering full doses of study drugs as calculated by the BSA. Obese patients will be treated based on actual body weight. Obese patients treated with full doses based on actual BSA are eligible * Is a pregnant or breastfeeding woman * Is deemed unable to comply with requirements of study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease-free Survival (DFS) Rate at 2 Years in TOP2A-amplified and in TOP2A-nonamplified HER2+ ESBC Patients Treated With TC+H. | 2 years | DFS was measured from the date of registration to either the date the patient was first recorded as having disease recurrence, or the date of death due to any causes before recurrence. If a patient had not recurred or died, DFS was censored at the date of last follow-up. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) Rate at 2 Years in TOP2A-amplified and in TOP2A-nonamplified HER2+ ESBC Patients Treated With TC+H. | 2 years | OS is measured from the date of registration to the date of death for a dead patient. If a patient is still alive or is lost to follow up, the patient will be censored at the last contact date. |
| DFS by cMyc Expression in This Population of HER2+ ESBC Patients Treated With TC+H. | 2 years | DFS was measured from the date of registration to either the date the patient was first recorded as having disease recurrence, or the date of death due to any causes before recurrence. If a patient had not recurred or died, DFS was censored at the date of last follow-up. |
| OS by cMyc Expression in This Population of HER2+ ESBC Patients Treated With TC+H. | 2 years | OS is measured from the date of randomization to the date of death for a dead patient. If a patient is still alive or is lost to follow up, the patient will be censored at the last contact date. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TC+H docetaxel (Taxotere), plus cyclophosphamide (Cytoxan), plus weekly trastuzumab (Herceptin) | 493 |
| Total | 493 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 44 |
| Overall Study | Disease Progression | 1 |
| Overall Study | Investigator Request | 2 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Other | 13 |
| Overall Study | Patient Request | 21 |
Baseline characteristics
| Characteristic | TC+H |
|---|---|
| Age, Continuous | 55.1 years STANDARD_DEVIATION 10.1 |
| Race/Ethnicity, Customized Asian | 12 participants |
| Race/Ethnicity, Customized Black | 36 participants |
| Race/Ethnicity, Customized Caucasian | 414 participants |
| Race/Ethnicity, Customized Hispanic | 27 participants |
| Race/Ethnicity, Customized Indian | 1 participants |
| Race/Ethnicity, Customized Other | 3 participants |
| Region of Enrollment United States | 493 participants |
| Sex: Female, Male Female | 493 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 481 / 486 |
| serious Total, serious adverse events | 51 / 486 |
Outcome results
Primary
Disease-free Survival (DFS) Rate at 2 Years in TOP2A-amplified and in TOP2A-nonamplified HER2+ ESBC Patients Treated With TC+H.
DFS was measured from the date of registration to either the date the patient was first recorded as having disease recurrence, or the date of death due to any causes before recurrence. If a patient had not recurred or died, DFS was censored at the date of last follow-up.
Time frame: 2 years
Population: ITT population. Patients were excluded if their TOP2A amplification were unknown.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TOP2A-amplified Group | Disease-free Survival (DFS) Rate at 2 Years in TOP2A-amplified and in TOP2A-nonamplified HER2+ ESBC Patients Treated With TC+H. | 0.978 probability of disease-free survival |
| TOP2A-nonamplified Group | Disease-free Survival (DFS) Rate at 2 Years in TOP2A-amplified and in TOP2A-nonamplified HER2+ ESBC Patients Treated With TC+H. | 0.979 probability of disease-free survival |
Secondary
DFS by cMyc Expression in This Population of HER2+ ESBC Patients Treated With TC+H.
DFS was measured from the date of registration to either the date the patient was first recorded as having disease recurrence, or the date of death due to any causes before recurrence. If a patient had not recurred or died, DFS was censored at the date of last follow-up.
Time frame: 2 years
Population: ITT population. Patients were excluded if their cMYC amplification were unknown.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TOP2A-amplified Group | DFS by cMyc Expression in This Population of HER2+ ESBC Patients Treated With TC+H. | 0.968 probability of disease-free survival |
| TOP2A-nonamplified Group | DFS by cMyc Expression in This Population of HER2+ ESBC Patients Treated With TC+H. | 0.981 probability of disease-free survival |
Secondary
OS by cMyc Expression in This Population of HER2+ ESBC Patients Treated With TC+H.
OS is measured from the date of randomization to the date of death for a dead patient. If a patient is still alive or is lost to follow up, the patient will be censored at the last contact date.
Time frame: 2 years
Population: ITT population. Patients were excluded if their cMYC amplification were unknown.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TOP2A-amplified Group | OS by cMyc Expression in This Population of HER2+ ESBC Patients Treated With TC+H. | 0.990 probability of overall survival |
| TOP2A-nonamplified Group | OS by cMyc Expression in This Population of HER2+ ESBC Patients Treated With TC+H. | 0.991 probability of overall survival |
Secondary
Overall Survival (OS) Rate at 2 Years in TOP2A-amplified and in TOP2A-nonamplified HER2+ ESBC Patients Treated With TC+H.
OS is measured from the date of registration to the date of death for a dead patient. If a patient is still alive or is lost to follow up, the patient will be censored at the last contact date.
Time frame: 2 years
Population: ITT population. Patients were excluded if their TOP2A amplification were unknown.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TOP2A-amplified Group | Overall Survival (OS) Rate at 2 Years in TOP2A-amplified and in TOP2A-nonamplified HER2+ ESBC Patients Treated With TC+H. | 0.995 probability of overall survival |
| TOP2A-nonamplified Group | Overall Survival (OS) Rate at 2 Years in TOP2A-amplified and in TOP2A-nonamplified HER2+ ESBC Patients Treated With TC+H. | 0.988 probability of overall survival |